Patient Safety and Quality

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Faster new drug review is linked to more adverse drug reactions

The recent withdrawal from the market of several high-profile new drugs because of safety concerns has led some observers to wonder whether the faster review process for new drugs by the Food and Drug Administration (FDA) might be contributing to an increase in serious adverse drug reactions (ADRs)-including hospitalization and death. A new study found a link between the two. Nevertheless, this risk must be weighed against a drug's benefits, asserts study author Mary K. Olson, Ph.D., of Tulane University.

The Prescription Drug User Fee Act (PDUFA), which became law on October 29, 1992, sought to speed up the process of bringing new drugs to market by giving the FDA additional resources (via user fees paid by the pharmaceutical companies), while setting deadlines of 6 months for consideration of priority-rated drug applications (drugs deemed therapeutically novel by the FDA) and 12 months (now 10 months) for other new drugs.

Dr. Olson examined the links between the speed of FDA approval, industry user fees, drug novelty, and other important determinants on ADRs. She used data on new drug approvals by the FDA, on ADRs reported to the FDA by clinicians and patients, the degree of use of these new drugs within 2 years after their approval (taken from the Agency for Healthcare Research and Quality's Medical Expenditure Panel Surveys), and other factors to construct a model of drug-specific ADR counts.

The study focused on new chemical entities approved from 1990 to 2001. The 310 drugs included in the analysis had a total of 96,751 serious ADRs within 2 years after FDA approval-including 57,511 that required hospitalization and 17,797 ADRs that resulted in death. Mean review times for these drugs showed a declining pattern over the sample period. For example, new drugs approved from 1990 to 1992 had an average review time of 31 months while drugs approved in 1996 to 2001 had a mean review time under 17 months.

Eighty-one percent of the drugs were approved after PDUFA passage, including 69 percent submitted after the Act became law. Therapeutically novel drugs comprised 42 percent of the approved drugs. Faster drug review times were significantly associated with increased numbers of serious ADRs, ADR hospitalizations, and ADR deaths.

A 10-month reduction in review time was associated with a 12 percent increase in serious ADRs reported during the first 2 years after FDA approval, an 11 percent increase in ADR hospitalizations, and an 11 percent increase in ADR deaths. More ADRs were associated with novel drugs, drugs having a black box warning, and drugs for AIDS, bacterial infections, other infections, cancer, epilepsy, arthritis, and mental health conditions, as well as anesthetics.

After controlling for the effects of review speed, user fee approvals and submissions showed little association with ADRs, which suggests that PDUFA's impact on drug-related risks occurs primarily through the speed of review. The study was funded in part by the Agency for Healthcare Research and Quality (HS13932).

More details are in "The risk we bear: The effects of review speed and industry user fees on new drug safety," by Dr. Olson, in the March 2008 Journal of Health Economics 27, pp. 175-200.